Randomized clinical trial of folate supplementation in patients with peripheral arterial disease

Khandanpour, Nader; Armon, Matthew P.; Jennings, Barbara; Finglas, Paul; Willis, Gavin; Clark, Allan; Meyer, Felicity J.

doi:10.1002/bjs.6670

Cited by 26 publications

(50 citation statements)

References 31 publications

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“…Although drugs and surgical procedures that target diseases of the elderly will hopefully arrest or partially reverse tissue damage caused by aging and chronic stress, measures to maintain health are arguably a better approach to lengthening our healthy life span. Most dietary supplement programs include combinations of vitamins, antioxidants, and other constituents, some of which have been shown to have significant health benefits in controlled clinical studies, whereas others may show adverse effects, [1][2][3][4][5][6] underscoring the need to assess functional effects of combination products. This paper presents initial data from an ongoing observational study of a novel dietary supplement program, PattonProtocol-1, which includes a natural product-derived telomerase activator targeting a fundamental aspect of cellular aging.…”

mentioning

confidence: 99%

A Natural Product Telomerase Activator As Part of a Health Maintenance Program

Harley

Liu²,

Blasco³

et al. 2011

Rejuvenation Research

156

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Most human cells lack sufficient telomerase to maintain telomeres, hence these genetic elements shorten with time and stress, contributing to aging and disease. In January, 2007, a commercial health maintenance program, PattonProtocol-1, was launched that included a natural product-derived telomerase activator (TA-65 Ò , 10-50 mg daily), a comprehensive dietary supplement pack, and physician counseling/laboratory tests at baseline and every 3-6 months thereafter. We report here analysis of the first year of data focusing on the immune system. Low nanomolar levels of TA-65Ò moderately activated telomerase in human keratinocytes, fibroblasts, and immune cells in culture; similar plasma levels of TA-65 Ò were achieved in pilot human pharmacokinetic studies with single 10-to 50-mg doses. The most striking in vivo effects were declines in the percent senescent cytotoxic (CD8 þ /CD28 À ) T cells (1.5, 4.4, 8.6, and 7.5% at 3, 6, 9, and 12 months, respectively; p ¼ not significant [N.S.], 0.018, 0.0024, 0.0062) and natural killer cells at 6 and 12 months ( p ¼ 0.028 and 0.00013, respectively). Most of these decreases were seen in cytomegalovirus (CMV) seropositive subjects. In a subset of subjects, the distribution of telomere lengths in leukocytes at baseline and 12 months was measured. Although mean telomere length did not increase, there was a significant reduction in the percent short (<4 kbp) telomeres ( p ¼ 0.037). No adverse events were attributed to PattonProtocol-1. We conclude that the protocol lengthens critically short telomeres and remodels the relative proportions of circulating leukocytes of CMV þ subjects toward the more ''youthful'' profile of CMV À subjects. Controlled randomized trials are planned to assess TA-65 Ò -specific effects in humans.

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mentioning

confidence: 99%

A Natural Product Telomerase Activator As Part of a Health Maintenance Program

Harley

Liu²,

Blasco³

et al. 2011

Rejuvenation Research

156

View full text Add to dashboard Cite

show abstract

“…Third, we acknowledge that the follow-up period of 2 years is relatively short for cardiovascular outcome parameters. Our study was designed to study the effect of vitamin B12 and folic acid supplementation on PWV, and for this parameter, a 2-year intervention is considered to be sufficient, because PWV is known to respond quickly as other trials with PWV as outcome variable have shown [8,29,30]. Nevertheless, arterial stiffness is known for its limited reversibility and therefore it cannot be ruled out that differences in PWV levels may have been detected when using a longer intervention period.…”

Section: Discussionmentioning

confidence: 98%

Effects of 2-year vitamin B12 and folic acid supplementation in hyperhomocysteinemic elderly on arterial stiffness and cardiovascular outcomes within the B-PROOF trial

Enneman²,

Km³

et al. 2015

Journal of Hypertension

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“…This observation demonstrated that the improvement in endothelial function is due to direct pharmacologic actions of folic acid rather than reductions inHcy concentrations [32] . Another folate study performed more recently confirmed that daily supplementation of oral folic acid improves arterial function in patients with peripheral arterial disease [33] . Concerning this, a randomized study conducted in 103 patients at increased risk of stroke, investigated the effect of folic acid supplementation on carotid intima-media thickness (IMT).…”

Section: Stroke --+ +mentioning

confidence: 96%

High Homocysteine Serum Levels as A Cause of Early and Massive Atherosclerosis: Vitamins B-6-9-12 Supplementation: More Shadows Than Lights

Cacciapuoti

2016

Journal of Cardiology and Therapy

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addition, some experiences performed in this field demonstrated that these nutrients could favor some negative effects, as the growth of an unknown neoplastic mass, especially the cells of prostate cancer. Therefore, the supplementation with folates and other vitamins of B group can be performed cautiously in patients with increased Hcy serum concentration. INTRODUCTIONApart from traditional risk factors for cardiovascular disease, a powerful cause for raised cardiovascular morbility and mortality can be the inherited or acquired hyper-homocysteinemia (H-Hcy). In this field, several reports referred that H-Hcy can be responsible for early and massive atherosclerosis, inducing some vascular diseases life threatening, such as myocardial infarction (MI), ischemic acute stroke (IS), and peripheral vascular disease (PVD) [1][2][3][4][5] . Concerning this, several studies and trials demonstrated that elevated plasma total Hcy may promote atherothrombosis with several mechanisms [6][7][8] . Among these, increased Hcy and S-adenosyl-homocysteine (SAH) serum values, inhibiting the methyltransferases, result in abnormal smooth muscle cell proliferation and reduction of endothelial cells' growth. A critical role in the atherosclerotic process is played by DNA hypomethylation [9,10] . But, H-Hcy also causes down regulation of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), resulting in depletion of H2S, an angiogenic agent with antioxidant and vasorelaxing properties. Therefore, its depletion results in ABSTRACTFolic acid and/or Vitamins B6-12 deficiency induces high-homocysteine (H-Hcy) serum levels for reduced activity of methylene-tetra hydro folate reductase (MTHFR). This metabolic derangement can be responsible for early and massive atherosclerosis, that could favour ischemic acute events. It can be assumed that vitamins' supplementation, reducing the elevated Hcy serum concentration, could reduce atherosclerotic risk. In this review,we evaluated if, the reduction of the high Hcy values by the B-vitamins' supplementation, is able to reduce the incidence of atherosclerotic events.Retrospective trials performed in patients already suffered of acute ischemic episodes, demonstrated that vitamins B6-9-12 supplementation was unable to reduce the incidence of new ischemic events, even if it lowers the high Hcy levels. On the contrary, perspective studies carried out in patients not previously suffered of cardiovascular acute events, evidenced that the vitamins' supplementation significantly reduced both Hcy serum concentration and atherosclerotic risk. These conflicting results demonstrate that folic acid and vitamins B6/12 supplementation is effective in to reduce high Hcy serum concentration in patients with signs of previous atherosclerosis, but is unable to reduce the atherosclerotic risk. On the contrary, the supplementation is useful in to lower both high Hcy serum levels and atherosclerotic risk in patients without atherosclerotic marks. In

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Randomized clinical trial of folate supplementation in patients with peripheral arterial disease

Abstract: Folate administration reduced plasma homocysteine, and slightly improved ABPI and bk-PWV.

Cited by 26 publications

References 31 publications

A Natural Product Telomerase Activator As Part of a Health Maintenance Program

A Natural Product Telomerase Activator As Part of a Health Maintenance Program

Effects of 2-year vitamin B12 and folic acid supplementation in hyperhomocysteinemic elderly on arterial stiffness and cardiovascular outcomes within the B-PROOF trial

High Homocysteine Serum Levels as A Cause of Early and Massive Atherosclerosis: Vitamins B-6-9-12 Supplementation: More Shadows Than Lights

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